Botulinum Toxin Injection With Prostate Brachytherapy
Keywords
Abstract
Description
Brachytherapy is a popular treatment modality for localized prostate cancer, where radioactive seeds are implanted through 18 gauge needles into the prostate via a perineal template with rectal ultrasound guidance. The radioactivity is delivered over several months, depending on the isotope used. During this time, there can be exacerbation of urinary voiding symptoms from early edema of the prostate gland due to the implantation procedure, then later from the inflammatory reaction of the radiation. Because the initial acute inflammation may persist for many months despite steadily declining doses of radiation, attempts are made to minimize urinary symptoms prior to brachytherapy with pharmacologic therapy (alpha-blockers) or minimally invasive surgical therapy (transurethral incision or limited transurethral resection to avoid significant distortion of the prostate parenchyma for future seed implantation). Even with these precautions, around 30-40% of brachytherapy patients will still develop voiding symptoms. With such bothersome symptoms, intervention is deferred for at least 8-10 months to avoid distorting the planned field of radiation. Once symptoms develop, various additional pharmacologic measures are employed, such as increased doses of alpha-blockers, medrol steroid taper, and non-steroidal anti-inflammatory agents. Some patients require intermittent self-catheterization or suprapubic catheter for urinary diversion.
Botulinum toxin has been used for cosmetic uses, and has been successfully used for treatment of overactive bladder, external sphincter dyssynergia, and benign prostatic hyperplasia (BPH). The studies with BPH show reduction in symptoms scores, PSA, and prostate volume, the latter from atrophy due to the denervation effect. The response lasts for 6-9 months.
We propose to study botox intraprostatic injection during brachytherapy to see whether this improves urinary symptoms or avoids need for urinary tract instrumentation over this 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds. We will also monitor PSA, and see if there is any measurable augmentation of PSA decline with botox + Brachytherapy vs Brachytherapy alone. We will randomize patients to botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) vs saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (25-50 mg per injection), just 5-10 mm proximal to the bladder neck.
Study design:
N= 60 (30 receive Botox, 30 receive saline)
Followup:
AUA Symptoms scores weekly for 4 weeks, monthly thereafter Medications for urinary symptoms Need for catheterization PSA checked at 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo
Dates
Last Verified: | 10/31/2013 |
First Submitted: | 05/18/2008 |
Estimated Enrollment Submitted: | 05/19/2008 |
First Posted: | 05/20/2008 |
Last Update Submitted: | 11/18/2013 |
Last Update Posted: | 11/20/2013 |
Estimated Primary Completion Date: | 06/30/2012 |
Estimated Study Completion Date: | 06/30/2012 |
Condition or disease
Intervention/treatment
Drug: A
Drug: B
Phase
Arm Groups
Arm | Intervention/treatment |
---|---|
Experimental: A Botox injection | Drug: A Intraprostatic injection of Botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) administering 2 transperineal injections into both lateral lobes of the prostate (25-50 units per injection), just 5-10 mm proximal to the bladder neck. |
Placebo Comparator: B Saline injection | Drug: B Saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (1-2 cc per injection), just 5-10 mm proximal to the bladder neck. |
Eligibility Criteria
Ages Eligible for Study | 18 Years To 18 Years |
Sexes Eligible for Study | Male |
Accepts Healthy Volunteers | Yes |
Criteria | Inclusion Criteria: - Biopsy proven prostate cancer undergoing brachytherapy Exclusion Criteria: - Prior allergic reaction to botulinum toxin |
Outcome
Primary Outcome Measures
1. Urinary symptoms [Weekly for 4 weeks, monthly thereafter until 1 year]
Secondary Outcome Measures
1. PSA [1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo]